PMID- 30348619
OWN - NLM
STAT- MEDLINE
DCOM- 20190726
LR  - 20200301
IS  - 1938-0674 (Electronic)
IS  - 1533-0028 (Print)
IS  - 1533-0028 (Linking)
VI  - 18
IP  - 1
DP  - 2019 Mar
TI  - Fluoropyrimidine Cardiotoxicity: Time for a Contemporaneous Appraisal.
PG  - 44-51
LID - S1533-0028(18)30348-7 [pii]
LID - 10.1016/j.clcc.2018.08.001 [doi]
AB  - INTRODUCTION: Fluoropyrimidines (FPDs) are a fundamental component of many 
      chemotherapy regimens. Cardiotoxic adverse events (AEs) such as angina, ischemia, 
      arrhythmias, and cardiomyopathy associated with 5-fluorouracil (5-FU) and 
      capecitabine (CAPE) have been sparingly described in studies, primarily through 
      case reports. Data from the 1990s revealed an estimated incidence of 0.5% to 19%, 
      with cardiovascular fatalities occurring in </=28%. The current use of FPDs 
      includes multiple dosing regimens, oral or intravenous delivery, and 
      administration with additional cardiotoxic therapies. As such, it is imperative 
      to better define the cardiotoxicity risk in the modern treatment era. We 
      comprehensively evaluated the incidence, prevalence, and ascertainment of 
      cardiovascular risk factors and disease within ECOG-ACRIN (Eastern Cooperative 
      Group Cancer Research Group - American College of Radiology Imaging Network) 
      Cancer Research Group clinical trials incorporating 5-FU and CAPE. MATERIALS AND 
      METHODS: Case report forms and clinical study reports from the ECOG-ACRIN Cancer 
      Research Group database of phase II and III clinical trials incorporating 5-FU 
      and CAPE were evaluated. A total of 16 trials from 2002 to 2017 were identified 
      that had used bolus 5-FU (n = 1), continuous infusion 5-FU (n = 10) or CAPE (n = 
      5). RESULTS: A history of cardiovascular disease was variably defined and was an 
      exclusion criterion in 13 of the 16 studies (81%). The baseline risk factors and 
      history of cardiac disease were specifically collected in only 3 studies (19%). 
      All studies collected cardiovascular AEs using the Common Terminology Criteria 
      for Adverse Events version available at the time of the study. Fewer than half (7 
      of 16; 44%) of the study case report forms had also specifically requested 
      information on cardiac ischemia/infarction. In the 12 completed studies with 
      clinical study reports, the following AEs were reported: dyspnea, </=16%; 
      arrhythmias, </=6%; and angina, ischemia, and elevated troponin, </=5%. Some trials 
      only recorded cardiac AEs that were possibly associated with the novel drug being 
      studied and not those attributed to the standard of care in the 5-FU/CAPE arm, 
      further decreasing the numerical incidence. CONCLUSION: Inconsistent clinical 
      trial reporting of cardiac AEs precluded accurate and precise delineation of the 
      epidemiology of FPD-related cardiovascular AEs. Prospective knowledge of the 
      definition and natural history will lead to the development of risk factor 
      stratification and prechemotherapy interventions to reduce or prevent 
      cardiotoxicity. We propose that the prospective collection of baseline cardiac 
      data and prespecified cardiac endpoints are necessary to fully understand the 
      incidence and cardiac risk of FDPs.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Upshaw, Jenica N
AU  - Upshaw JN
AD  - Department of Medicine, Division of Cardiology, Tufts Medical Center, Boston, MA. 
      Electronic address: jupshaw@tuftsmedicalcenter.org.
FAU - O'Neill, Anne
AU  - O'Neill A
AD  - Department of Biostatistics and Computational Biology, Dana Farber Cancer 
      Institute- Eastern Cooperative Group Cancer Research Group - American College of 
      Radiology Imaging Network, Boston, MA.
FAU - Carver, Joseph R
AU  - Carver JR
AD  - Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA.
FAU - Dimond, Eileen P
AU  - Dimond EP
AD  - Division of Cancer Prevention, National Cancer Institute, Bethesda, MD.
FAU - Denlinger, Crystal S
AU  - Denlinger CS
AD  - Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA.
FAU - Kircher, Sheetal M
AU  - Kircher SM
AD  - Northwestern University, Chicago, IL.
FAU - Wagner, Lynne I
AU  - Wagner LI
AD  - Wake Forest University Health Sciences, Winston Salem, NC.
FAU - Ky, Bonnie
AU  - Ky B
AD  - Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA; Penn Cardiovascular Institute, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, PA.
FAU - Brell, Joanna M
AU  - Brell JM
AD  - Division Hematology/Oncology Case, Department of Medicine, MetroHealth Cancer 
      Center, Western Reserve University, Cleveland, OH.
LA  - eng
GR  - UG1 CA233320/CA/NCI NIH HHS/United States
GR  - UG1 CA233234/CA/NCI NIH HHS/United States
GR  - UG1 CA189828/CA/NCI NIH HHS/United States
GR  - U10 CA180820/CA/NCI NIH HHS/United States
GR  - U10 CA180794/CA/NCI NIH HHS/United States
GR  - U10 CA180853/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180820
PL  - United States
TA  - Clin Colorectal Cancer
JT  - Clinical colorectal cancer
JID - 101120693
RN  - 6804DJ8Z9U (Capecitabine)
RN  - U3P01618RT (Fluorouracil)
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects
MH  - Capecitabine/administration & dosage
MH  - Cardiotoxicity
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Fluorouracil/administration & dosage
MH  - Follow-Up Studies
MH  - Heart Diseases/epidemiology/*etiology/pathology
MH  - Humans
MH  - Incidence
MH  - Neoplasms/*drug therapy/pathology
MH  - Prognosis
MH  - United States/epidemiology
PMC - PMC6927029
MID - NIHMS1504281
OTO - NOTNLM
OT  - 5-Fluorouracil
OT  - Acute coronary syndrome
OT  - Capecitabine
OT  - Cardiac risk factors
OT  - Chest pain
EDAT- 2018/10/24 06:00
MHDA- 2019/07/28 06:00
PMCR- 2020/03/01
CRDT- 2018/10/24 06:00
PHST- 2018/07/17 00:00 [received]
PHST- 2018/08/08 00:00 [revised]
PHST- 2018/08/11 00:00 [accepted]
PHST- 2018/10/24 06:00 [pubmed]
PHST- 2019/07/28 06:00 [medline]
PHST- 2018/10/24 06:00 [entrez]
PHST- 2020/03/01 00:00 [pmc-release]
AID - S1533-0028(18)30348-7 [pii]
AID - 10.1016/j.clcc.2018.08.001 [doi]
PST - ppublish
SO  - Clin Colorectal Cancer. 2019 Mar;18(1):44-51. doi: 10.1016/j.clcc.2018.08.001. 
      Epub 2018 Aug 20.